This proposal continues the proof-of-concept development and testing of a novel, safe, and effective treatment device for onychomycosis (nail fungal infection). While onychomycosis is considered a cosmetic problem, the infected nail also becomes a persistent reservoir for infectious microbes that could lead to other significant medical problems. Over 35 million Americans suffer from onychomycosis, which carries a direct cost of over $4 billion in the US healthcare system. The device under development would offer patients and doctors a reliable method to treat nail fungal infections without toxic side effects unlike current oral medications that may cause liver damage, or topical creams and lasers that have low or unproven efficacy. In this project, we will develop a medical device prototype based on our patent pending technology to prove the feasibility of killing fungal infections through a human nail. Our critical success metric for this Phase I project is demonstration of the fungicidal effect of the instrument by 99.9% growth inhibition of both T. rubrum and T. mentagrophytes fungus through a human nail. This is a necessary step to reduce technical risk in the ultimate development of an FDA- approved medical device for curing onychomycosis. In support of our product goal, we propose to answer three critical questions related to the utility of this novel device: 1) Can performing simultaneous ultrasound and plasma treatment with an improved instrument prototype increase the antifungal properties of the treatment?; 2) Does the three dimensional curvature of a human cadaver nail change the needed treatment protocol vs. a flat surface?; 3) Will the antifungal effect of this treatment continue as additional fungal species are presented for treatment?